Potassium Iodide → tert-Butyl 3-{3-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]5-chloro-2-methoxy-6-methylphenyl}azetidine-1-carboxylate

HRID 1499714Notes

Reaction equation

HRID 1499714 reaction equation
[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+].[Cl:21][C:22]1[C:23]([CH3:44])=[C:24]([CH:33]2[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:34]2)[C:25]([O:31][CH3:32])=[C:26]([CH:28](Cl)[CH3:29])[CH:27]=1>CN(C)C=O.O>[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[CH:10]=[CH:9][N:8]([CH:28]([C:26]3[C:25]([O:31][CH3:32])=[C:24]([CH:33]4[CH2:34][N:35]([C:37]([O:39][C:40]([CH3:42])([CH3:41])[CH3:43])=[O:38])[CH2:36]4)[C:23]([CH3:44])=[C:22]([Cl:21])[CH:27]=3)[CH3:29])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 57067884-aminopyrido[2,3-d]pyrimidin-5(8H)-oneHCID 86677627tert-Butyl 3-[3-chloro-5-(1-chloroethyl)-6-methoxy-2-methylphenyl]azetidine-1-carboxylate

Product 1

HCID 86677653tert-Butyl 3-{3-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]5-chloro-2-methoxy-6-methylphenyl}azetidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a mixture of 4-aminopyrido[2,3-d]pyrimidin-5(8H)-one (from VWR) (8.6 mg, 0.053 mmol), cesium carbonate (26 mg, 0.080 mmol) and potassium iodide (0.89 mg, 0.0053 mmol) in N,N-dimethylformamide (0.2 mL) was added tert-butyl 3-[3-chloro-5-(1-chloroethyl)-6-methoxy-2-methylphenyl]azetidine-1-carboxylate (20 mg, 0.05 mmol, from Example 1, step 5, racemic intermediate). The mixture was stirred at 140° C. for 1 hour, then cooled and was diluted with water, extracted with ether. The organic layers were dried over MgSO4 and concentrated to afford the crude product which was used in the next step directly. LCMS calculated for C25H31ClN5O4 (M+H)+: m/z=500.2; Found: 500.1.

Workup

  1. temperaturecooled
  2. extractionextracted with ether
  3. dry with materialThe organic layers were dried over MgSO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-a622b0ccd441437690dffc798926c91e
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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